The Solid Tumour Group headed by Associate Professor Tim Price began work at The Queen Elizabeth Hospital in 2007 and moved to new laboratories in the Basil Hetzel Institute in 2009. In 2014, the group incorporated the newly established SAHMRI Colorectal Node, and now works on a comprehensive program in colorectal cancer spanning prevention, biology and treatment.

Identification, development and clinical trial of new therapeutic agents for the treatment of colorectal cancer

Development of new cancer biomarkers of drug resistance and therapeutic targets

Further understanding of the molecular mechanisms underlying colorectal cancer

Research Projects suitable for Honours and Postgraduate research students

Investigation of circulating DNA mutations in colorectal cancer (CRC)

Circulating tumour-derived DNA (ctDNA) may be present in plasma samples from patients with CRC, and the concentration level has been inversely correlated with survival outcome. It’s thought the ctDNA is derived from circulating tumour cells (CTC) yet there are reports of cases in which ctDNA was detected but no CTC were detectable (Bettegowda et al., 2014), suggesting that tumour DNA could be released from tumour exosomes in the circulation. ctDNA from plasma (liquid biopsy) provides a means to analyse tumour mutations to enable more sensitive disease monitoring. This means that disease recurrence or progression would be detected at an earlier time-point than would be possible with CT/PET imaging. CTCs will also be identified in collaboration with Prof Thierry at Uni SA and correlated with ctDNA findings. Techniques include DNA isolation from plasma, digital droplet PCR, mutation or methylation analysis, statistical survival and correlative analyses.

Role of aquaporins 1 and 5 in tumour angiogenesis in colon or breast cancer (2 projects)

Aquaporins (AQPs) are water channel proteins involved in cellular water flux, and implicated in migration, angiogenesis and metastasis in cancer. The drug discovery program in Professor Yool's lab has identified several drugs that modulate aquaporin channel activity. We have found that several of these drugs are effective in vitro at reducing migration and invasion of colon cancer cells and preventing angiogenesis (tumour blood vessel formation). We aim to investigate the efficacy of these drugs in inhibiting angiogenesis in vitro and in halting metastasis in pre-clinical mouse models of human colon or breast cancer. Our hypothesis is that tumour cells that lack AQP1 activity are unable to respond to hypoxia which drives angiogenesis. We will also establish a biobank of organoids cultured from metastatic breast biopsies for research work, in assessing the response to different novel therapeutic drugs in culture, and in characterising the mutational landscape and how that changes with developing resistance. A biobank of metastatic breast organoids is a much needed resource for future research which is currently lacking in this state. Techniques include cell culture, CRISPR gene knockout, RT-PCR, western blotting, functional assays of cell proliferation, invasion, migration, and angiogenesis and mouse models of human cancer.

Determination of resistance biomarkers in tumour tissue from patients undergoing therapy with anti-VEGF

MicroRNA expression platform will be used in correlative studies on archival tissue to identify biomarkers of resistance to bevacizumab (anti-VEGF monoclonal antibody). Techniques will include DNA and RNA/microRNA isolation from tissue blocks, running microRNA profiles, bioinformatics, and statistical analysis.

Within the SAHMRI Colorectal Node (based at the BHI), the South Australian Young Onset Colorectal Cancer Study (SAYO) is a hospital-based research program for identifying the causes and consequences of colorectal (bowel) cancer in young adults. The program has an ongoing registry for research participants and an associated database, with topics spanning genetics, pathology, and psychosocial aspects of this condition. The group consists of a research fellow, medical oncologist and hospital scientist. In addition, a network of collaborators contribute to research directions, analysis and outcomes of the project.

Research Projects suitable for Honours and Postgraduate Students

Early Onset Colorectal Cancer and Metabolic Syndrome

Our preliminary evidence suggests that the increase in incidence of colorectal (bowel) cancer in young adults may be related to the rising rate of metabolic syndrome components in the young adult population.In this study we will explore the overlap of genetic predispositions to both CRC and diabetes in young adults with pre-malignant polyps, or cancer.We will use pedigree analysis, next generation sequencing of the germline, and detailed epigenetic assays of colorectal tissue to identify markers of risk for CRC in the young adult population. It is our long-term objective to help identify at-risk young individuals in primary healthcare settings.

Medical and Psychosocial Aspects of Colorectal Cancer in Young Adults

Colorectal cancer (CRC or bowel cancer) is a common malignancy of older adults.However, over 1100 Australians under the age of 50 develop CRC each year, and the incidence of young onset disease has been rising in Australia and other Western countries during recent decades. Young adults with CRC suffer significant mortality and morbidity in the most productive time of their life. In this project, which would suit a psychology or nursing student, we will undertake a comprehensive study of the medical and psychosocial aspects of having CRC as a young adult. This will include the risk factors such as personal or family history of diabetes, family history of CRC, the diagnostic journey of the patient (since the majority of young patients present late in the course of their disease), and the life impacts post diagnosis on family and relationships, career and education, and physical and mental health.

Identification and characterisation of fibroblast subsets using single cell RNA-sequencing to improve outcomes in patients with rectal cancer

Please contact Dr Eric Smith to discuss this project further.
Project description: Preoperative (neoadjuvant) chemoradiotherapy (nCRT) followed by surgery is widely accepted as the standard of care for patients with rectal cancer. However, most will endure nCRT without clear benefit because currently there is no way to predict which patients will respond. Identification of non-responders before treatment would be enormously beneficial. They would not be at risk of the side effects, and surgery or alternative treatments could be undertaken without unnecessary delay. Significantly, an improved understanding of the factors associated with nCRT resistance could lead to identification of novel targets for intervention and suggest new avenues of research.
This project will investigate the role of cancer associated fibroblasts in the response to nCRT using a combination of innovative and emergent methodologies including single cell RNA-sequencing, multicolour fluorescence immunohistochemistry, and a range of fibroblast-cancer cell co-culture experimental models to identify, characterise and validate novel fibroblast subsets.
Projects available for: Honours / HDR / Masters / Mphil
Location: Basil Hetzel Institute, The Queen Elizabeth Hospital
Research project start: Semester 1 and 2
Special requirements: None